HYDROXYL RADICALS ARE INVOLVED IN THE OXIDATION OF ISOLATED AND CELLULAR DNA BASES BY 4-AMINOLEVULINIC ACID

5-Aminolevulinic acid (ALA) is a heme precursor, pathological accumula tion of which is associated with liver cancer, We show that the reacti ve oxygen species produced upon ALA metal-catalyzed oxidation promote the formation of several radical-induced base degradation products in isolated DNA. The distribution of modified bases is similar to that ob tained upon gamma irradiation. This observation strongly suggests the involvement of hydroxyl radicals in the ALA-mediated DNA damage. Incre ased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 5-hydroxy-2'-de oxycytidine in organ DNA of rats chronically treated with ALA were obs erved. This is strongly suggestive of the implication of hydroxyl radi cals in the ALA-induced degradation of cellular DNA. (C) 1998 Federati on of European Biochemical Societies.